Decreased expression of cell polarity protein Scribble correlated with altered subcellular localization of the Crumbs homologue 3 protein in human adenomyotic endometrial cells.

Abstract

Previous studies have revealed that loss of cell apical-basal polarity contributed to the early stages of tumorigenesis. Adenomyosis involves a down-growth and aberrant implantation of the endometrial basalis into the myometrium. This study discovered aberrant expression of polarity protein Scribble (Scrib) and Crumbs homologue 3 protein (CRB3) in epithelial cells of diffuse adenomyosis. This was a case-controlled study, including 39 patients with histologic evidence of adenomyosis, and 48 patients with carcinoma in situ of the uterine cervix without adenomyosis or endometriosis as control. Adenomyotic foci, eutopic endometrium of adenomyotic patients as well as normal endometrium were collected. Reverse Transcription Polymerase Chain Reaction (RT-PCR), Immunoreactivity, confocal microscopy and immune electron microscopy were conducted to evaluate Scribble expression and localization of Scribble and CRB3. Scrib was screen out as an abnormally expressed polarity protein in adenomyotic eutopic endometrium (ADM-EU) at messenger RNA (mRNA) level. The ADM-EU and adenomyotic ectopic endometrium showed a significantly decreased expression of Scrib compared with normal endometrium (all P-values <0.05). Scrib decreased significantly in ADM-EU than normal endometrium only in patients at proliferative phase and with severe dysmenorrhea (P-values <0.01, P-values <0.001 respectively). In ADM-EU, Scrib expression significantly lowered in patients with severe dysmenorrhea than mild dysmenorrhea (P-values <0.05). Aberrant redistribution of CRB3 from apical to basal lateral membrane portion was also detected in experiments by confocal microscopy immune electron microscopy (all P-values <0.01). Basolateral polarity protein Scrib was found decreased significantly in endometrial cells of adenomyosis at mRNA and protein level, compared with normal endometrium. Menstrual phase and severity of dysmenorrhea has an impact on Scrib expression. Scrib decrease was accompanied by aberrant redistribution of CRB3 from apical to basal lateral membrane portion.